印记障碍,Nature Reviews Disease Primers

印记障碍（ImpDis）是一种以基因组印记紊乱为特征的先天性疾病。最常见的个体 ImpDis 是 Prader-Willi 综合征、Angelman 综合征和 Beckwith-Wiedemann 综合征。个体ImpDis具有相似的临床特征，如生长障碍和发育迟缓，但疾病具有异质性，关键临床表现往往非特异性，导致诊断困难。影响差异甲基化区域 (DMR) 的四种基因组和印记缺陷 (ImpDef) 可导致 ImpDis。这些缺陷影响印记基因的单等位基因和亲本特异性表达。DMR 内的调节及其功能后果主要是未知的，但印记基因和功能通路之间的功能串扰已经被识别出来，从而深入了解 ImpDefs 的病理生理学。ImpDis 的治疗是对症治疗。由于这些疾病很少见，因此缺乏靶向治疗；然而，个性化治疗正在开发中。了解 ImpDis 的潜在机制并改善这些疾病的诊断和治疗需要采用多学科方法并听取患者代表的意见。

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Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader–Willi syndrome, Angelman syndrome and Beckwith–Wiedemann syndrome. Individual ImpDis have similar clinical features, such as growth disturbances and developmental delay, but the disorders are heterogeneous and the key clinical manifestations are often non-specific, rendering diagnosis difficult. Four types of genomic and imprinting defect (ImpDef) affecting differentially methylated regions (DMRs) can cause ImpDis. These defects affect the monoallelic and parent-of-origin-specific expression of imprinted genes. The regulation within DMRs as well as their functional consequences are mainly unknown, but functional cross-talk between imprinted genes and functional pathways has been identified, giving insight into the pathophysiology of ImpDefs. Treatment of ImpDis is symptomatic. Targeted therapies are lacking owing to the rarity of these disorders; however, personalized treatments are in development. Understanding the underlying mechanisms of ImpDis, and improving diagnosis and treatment of these disorders, requires a multidisciplinary approach with input from patient representatives.